Magnesium is an essential mineral involved in numerous biochemical processes, including adenosine triphosphate (ATP) production, cellular signal transduction, DNA, RNA and protein synthesis, and bone formation (1)(2). Magnesium also helps regulate blood pressure and enzymes such as those that control intracellular calcium and potassium, and is essential for normal heart functioning (1)(3). Dietary magnesium can be found in many foods, and especially in dark green leafy vegetables, nuts, legumes, whole grains, fruits, and fish (4).

In dietary supplements, other over-the-counter products, and pharmaceutical preparations, magnesium is combined with another substance such as a salt or acid, and has specific therapeutic uses. Magnesium carbonate, magnesium hydroxide, and magnesium oxide are found in antacid and laxative products. Magnesium citrate is used as a laxative before diagnostic procedures or surgery of the colon. Magnesium chloride, magnesium gluconate, magnesium lactate, and magnesium sulfate are clinically used to treat magnesium deficiency.

Both dietary magnesium and magnesium supplementation have been studied widely for their potential role in chronic ailments such as heart disease and diabetes. Dietary magnesium intake is associated with reduced mortality from cardiovascular disease, especially for women (5). It is also associated with reduced risk of sudden cardiac death (SCD), although studies have been mixed and more affirmative for the effect of serum magnesium on SCD (6)(7). Dietary magnesium may help reduce the risk of ischemic stroke (8), metabolic syndrome (9)(10), type 2 diabetes (11) and insulin resistance (12), asthma (13), and osteoporosis (1), but study results are conflicting as to whether dietary magnesium can reduce depression (14)(15). Other studies also have not linked dietary magnesium with cancer incidence and mortality (16), or pancreatic cancer risk (17), but have associated higher intakes with a lower risk for colorectal tumors (18) and lung cancer (19). Additional studies are needed to confirm these effects.

Magnesium supplementation has been evaluated for a variety of health conditions. Oral magnesium may increase survival in patients with heart failure (20)(21), and improve insulin sensitivity in healthy adults (22). In a study of overweight individuals, magnesium supplementation resulted in changes in gene expression and other positive effects on metabolic pathways (23). Some studies have shown a reduction in blood pressure after magnesium supplementation (24)(25), but an earlier systematic review suggests the positive findings are due to poor trial design and short duration (26). Also in contrast, data from a large, community-based cohort did not show low serum magnesium to be a risk factor for developing hypertension or cardiovascular disease (27).

Other studies of oral supplements have demonstrated positive effects on bone mass accrual in healthy adolescents with inadequate magnesium intake (28), and suppressed bone turnover in postmenopausal osteoporotic women (29). In adults with asthma, magnesium improved objective measures of airway resistance and subjective measures of asthma control and quality of life (13); in pediatric patients with cystic fibrosis, it has improved respiratory muscle strength (30). There is also moderate evidence for its use in migraine headache and prophylaxis (31). Although preliminary clinical data have shown mixed results with oral magnesium for premenstrual syndrome (32), another pilot study has shown it reduces menopausal hot flashes in breast cancer patients (33), and a systematic review supports its use for leg cramps during pregnancy (34). More and larger studies are needed to elucidate conflicting results and clarify the roles for magnesium supplementation across various health conditions.

Many adults, particularly African-Americans (35) and the elderly (9), may not have adequate dietary intakes of magnesium. However, true magnesium deficiency most often occurs with critical illness including cardiac conditions and preeclampsia, as well as gastrointestinal and renal conditions, poorly-controlled diabetes, and alcoholism (3). In addition, certain medications including calcineurin inhibitors (36), high-dose antivirals (37), and the long-term use of proton pump inhibitors (38), as well as some cancer therapy regimens (39)(40) and surgical procedures (41)(42), may also cause hypomagnesemia. If magnesium deficiency is suspected, patients should be evaluated by their treating physician to determine the extent of inadequate intake and its effective management, as well as to avoid potential drug interactions or magnesium toxicity.

Hypermagnesemia is rare and results from failure to excrete magnesium or because of excessive intake. It may especially occur in patients with gastrointestinal or renal dysfunction, and have serious effects such as hypotension, bradycardia, depression of tendon reflexes, and other cardiovascular and neuromuscular manifestations (43)(44).

Magnesium plays a significant role in vascular and metabolic biology as well as numerous biochemical reactions. In vitro, magnesium negatively regulates vascular calcification and osteogenic differentiation through an increase or restoration of transient receptor potential melastatin 7 (TRPM7) activity and increased expression of anticalcification proteins (45). Magnesium also influences blood pressure levels through interactions with the renin-angiotensin system, by acting as a calcium channel blocker to reduce vascular resistance, and by modulating vascular tone and reactivity (46)(47). Further, it contributes to the homeostasis of electrolytes in cells via sodium-potassium pump activation (47) and can revert impaired intracellular ion homeostasis (25).

As a cofactor of all reactions involving ATP transfer, magnesium is a major determinant of insulin and glucose metabolism, critical to carbohydrate metabolism, and regulates the activity of all enzymes involved in phosphorylation reactions (48). These vascular and metabolic mechanisms are echoed by observed relationships between magnesium deficiency and oxidative stress, proinflammatory states, endothelial dysfunction, platelet aggregation, insulin resistance, and hyperglycemia (48)(49).

Magnesium can also serve an immunomodulatory function by regulating NF-kB activation and cytokine production, and limiting systemic inflammation (50). It also reduces markers for systemic inflammation and endothelial dysfunction including C-reactive protein (4)(51).

Magnesium salts are poorly absorbed, and act as an osmotic laxative by retaining water in the intestine. The mechanism by which magnesium may affect the bioavailability of concomitantly administered drugs is through the formation of insoluble chelate complexes with those drugs, substantially reducing their bioavailability (52).

Experimental and epidemiological evidence for the role of magnesium in cancer is conflicting. Its part in cellular metabolism and maintaining genetic stability, regulation of cell proliferation, and protections against insulin resistance, oxidative stress, and systemic inflammation are also cancer-preventive attributes (18)(19). At the same time, hypomagnesemia as a side effect of some cancer treatments may produce an inhibitory effect on tumor growth and neoangiogenesis, but magnesium levels are also increased in tumors both in vivo and in vitro, suggesting multiple and possibly dichotomous roles of magnesium in cancer (53)(54).

Absorption
The entire length of bowel can absorb magnesium (55), and bowel disorders may enhance magnesium absorption (43). About 30–40% of ingested magnesium is normally absorbed by the intestine and controlled by several factors, including the balance between intestinal absorption of available dietary magnesium and renal excretion of urinary magnesium. Approximately 90% of normal magnesium absorption occurs passively through the paracellular pathway. In contrast, transcellular magnesium absorption is an active process mediated by TRPM6 and TRPM7 magnesium transport proteins, and regulated by a number of hormones and other influences (56). In addition, there appears to be an inverse relationship with fractional absorption, resulting in increased absorption with dietary deficits and decreased absorption with magnesium surfeits (56).

Magnesium supplements are known to be poorly absorbed orally (26), and bioavailability generally depends on both the type of magnesium used and its form of administration (57). Oral magnesium supplements may use a combination of sources including citrate, glycinate, malate, and oxide, in an effort to increase bioavailability and absorption. Comparative bioavailability studies across different types of supplements are lacking. One study evaluating magnesium oxide 450 mg in both capsule and effervescent form found that magnesium bioavailability from capsules was 4.7% versus 9.5% for the effervescent tablets. This increase with the latter formulation is likely due to complete solubility of the magnesium salt as it is dissolved in water so that magnesium ionization, an important condition for absorption, occurs (57).

Distribution
Magnesium is rapidly distributed throughout the body following absorption. About 60% of plasma magnesium occurs as the free ion, with about 30% bound to albumin and 10% complexed to serum anions. Normal plasma magnesium concentration is 0.75 to 0.95 mmol/L or 1.5 to 1.9 mEq/L, but plasma levels often do not reflect total body magnesium content, and reference ranges among laboratories can vary. In addition, the diagnosis of health conditions reflecting altered magnesium content are more dependent on tissue rather than blood levels (55).

Metabolism/Excretion
The kidneys maintain magnesium balance by excreting absorbed magnesium. Both ionized and complexed magnesium (70% of serum magnesium) are freely filtered at the glomerulus, and magnesium homeostasis is achieved with variable rates of renal resorption (55).

Patients with heart block or severe renal disease should not take magnesium supplements. Those with other heart, kidney, or gastrointestinal disorders (44), should not take magnesium supplements without a doctor's supervision.

Hypermagnesemia due to ingestion of magnesium oxide by a 72-year-old woman with constipation and prolonged colonic retention caused prolonged hypotension and decreased perfusion, which led to hypoxic encephalopathy (44).

Aminoglycosides: Can cause renal magnesium wasting and subsequent deficiency (60).Antibiotics: Magnesium or antacids may reduce the absorption of fluoroquinolones, tetracyclines, and nitrofurantoin. Magnesium-containing products, if needed, should be taken in accordance with the prescribing information of these antibacterials (52)(61)(62).Anticoagulants: Magnesium or antacids can increase rate and extent of absorption (63).Antidiabetics: Magnesium or antacids can increase rate and extent of absorption of sulphonylurea drugs (63). Antifungals: Magnesium or antacids may reduce the rate and extent of itraconazole absorption (64).Antimicrobials (pentamidine): Can cause renal magnesium wasting and subsequent deficiency (60).Antivirals (ribavirin): High-dose antivirals may cause hypomagnesemia (37).Bisphosphonates: Calcium/magnesium levels may be affected in patients receiving bisphosphonate therapy (65). In addition, antacids may interfere with absorption of bisphosphonates (52).Calcineurin inhibitors: May cause hypomagnesemia (36).Calcium channel blockers: Magnesium may potentiate blood pressure-lowering effects (66).Cisplatin-based chemotherapy: May cause hypomagnesemia (39).Dasatinib: May increase blood levels of magnesium (67).Digoxin: Digoxin reduces tubular magnesium reabsorption. In patients with congestive heart failure effects may be cumulative with diuretics, diet, and poor intestinal absorption. Hypomagnesemia may increase adverse effects such as palpitations and nausea with digoxin. Magnesium and other electrolyte levels should be monitored in patients treated with cardiovascular drugs (68)(69).Diuretics: Loop and thiazide diuretics are electrolyte-depleting, and can cause renal magnesium wasting and subsequent deficiency (60). Cumulative effects with other cardiovascular drugs may occur (see Digoxin entry).Monoclonal antibodies (cetuximab, panitumumab): These cancer drugs target the epidermal-growth-factor receptor and hypomagnesemia is a frequent side effect (40). Electrolytes are monitored during and following treatment, and appropriate treatment instituted (70)(71).Neuromuscular blockers: Magnesium supplements may potentiate the effects of neuromuscular blockers used in clinical settings (72)(73).Nonsteroidal anti-inflammatory drugs: Antacids can increase rate and extent of absorption (63).Proton pump inhibitors: Long-term use may cause hypomagnesemia (38).Synthetic thyroid hormone: Two case reports of magnesium-containing antacids/laxatives reduced the effectiveness of levothyroxine (74).

Kass L, et al. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012;66:411-418.
This meta-analysis assessed the effect of magnesium supplementation on blood pressure using 22 trials and 23 sets of data (n=1173) with 3 to 24 weeks of follow-up. An overall effect of 0.36 and 0.32 was observed for diastolic blood pressure (DBP) and systolic blood pressure (SBP), respectively. A greater effect was seen for the intervention in crossover trials (DBP 0.47, SBP 0.51). Although not all individual trials showed significant BP reduction, combining all trials did show a decrease in SBP of 3 to 4 mmHg and DBP of 2 to 3 mmHg, which further increased with crossover trials and intakes >370 mg/day. In this meta-analysis, magnesium supplementation appears to achieve a small but clinically significant reduction in blood pressure. These findings should be confirmed in larger trials with solid methodology.

Park H, et al. A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients. Support Care Cancer. 2011;19:859-863.
This 4-week single arm study evaluated the effectiveness of magnesium supplements on menopausal hot flashes in 25 evaluable breast cancer patients with at least 14 hot flashes per week. All patients received magnesium oxide 400 mg for 4 weeks, with dose-escalation to 800 mg if needed. A total of 17 patients escalated the magnesium dose after 2 weeks of the starting dose. After 4 weeks of treatment, there was a 41.4% reduction in hot flash frequency per week (p=0.009), with a 50.4 % decrease in average weekly hot flash score (p=0.02). A >50% reduction in hot flash score was achieved by 14 (56%) patients, and 19 (76%) experienced a >25% reduction compared with baseline. Although there was no statistically significant effect on overall quality of life, there were significant reductions for the symptoms of fatigue, sweating, and distress. Side effects were minor and there was no significant difference in reported symptoms of headache, nausea, and diarrhea before and after treatment. Two women experienced grade 1 diarrhea and 2 patients discontinued treatment due to headache and nausea. Oral magnesium may be a potential therapy for menopausal hot flashes in breast cancer patients. Confirmatory randomized placebo-controlled trials are needed.

Consumer Information

How It Works

Bottom Line:There are many benefits to adequate intake of dietary magnesium.However, magnesiumsupplements may increase the risk of interactions with many drugs.

Magnesium plays many essential roles in the human body. Adequate magnesium intake can help prevent chronic ailments such as heart disease and diabetes, but its potential role in cancer prevention is unclear. Many adults may not get enough magnesium through diet, but a true magnesium deficiency most often occurs with serious illnesses. Certain medications can also cause magnesium deficiency. Magnesium products are also used as drugs for a variety of medical conditions, and treatment is carefully monitored to prevent serious side effects.

There are case reports of excess levels of magnesium due to supplements. Because magnesium supplements may interact with many drugs, and magnesium itself is a component of certain over-the counter drugs, supplements should be avoided in patients with heart, kidney, or gastrointestinal disorders. You should also inform your doctor of any over-the-counter products that you are taking which could contain magnesium.

To prevent diabetes
Magnesium supplements have been shown to improve insulin levels in overweight nondiabetic individuals, suggesting that adequate magnesium levels may help prevent the onset of diabetes. Larger studies are needed.

To help bone development or prevent weak bones
Small studies show that magnesium supplements have positive effects on bone development in adolescents and can prevent bone loss in postmenopausal women.

To prevent fatigue
There are no studies of oral magnesium supplements for chronic fatigue. A small study has shown that magnesium reduced fatigue symptoms in breast cancer patients with menopausal hot flashes.

To reduce hot flashes
A small study has shown that magnesium can reduce hot flashes with few side effects in breast cancer patients.

To improve premenstrual syndrome (PMS) symptoms
It is unclear whether magnesium can help premenstrual syndrome.

To prevent migraines
There is some evidence that magnesium can help prevent migraines, and several medical guidelines include magnesium as a potential therapy.

To relieve leg cramps
Some studies of moderate quality support the use of magnesium for leg cramps during pregnancy.

(Common Use) To relieve acid indigestion, heartburn, sour stomach, and constipation
Magnesium is an active ingredient in many over-the-counter preparations including laxatives and antacids. Many individuals may not realize that they are possibly getting magnesium from these common sources.

Lowering blood pressure
Results from studies on the ability of magnesium supplements to lower blood pressure have been mixed. An evaluation of 22 trials selected using specific criteria, known as a meta-analysis, reviewed the data to see whether there would be a more consistent overall finding. Even though there was a high level of variance among the study populations, and not all individual trials showed a significant reduction in blood pressure, this meta-analysis did find a small but significant reduction in blood pressure overall. More and larger studies are needed to confirm this finding.

Menopausal hot flashes in breast cancer patients
A very small and short-term trial, known as a pilot study, looked at the effectiveness of magnesium supplements on menopausal hot flashes in 25 breast cancer patients who had at least 14 hot flashes per week. After 4 weeks of treatment, there was a significant reduction in number of hot flashes per week, but no significant effect on overall quality of life, even though symptoms of fatigue, sweating, and distress were reduced. Side effects were minor and there was no difference in reported symptoms of headache, nausea, and diarrhea before and after treatment. These results should be confirmed in a randomized placebo-controlled trial.

To reduce insulin resistance in overweight nondiabetic subjects
A small double-blind, randomized, placebo-controlled study evaluated whether magnesium supplements could effect insulin sensitivity and other risk factors known as metabolic syndrome in 52 overweight, insulin-resistant, nondiabetics. Individuals who took a prescribed magnesium supplement for 6 months had significant improvements in fasting plasma glucose and some insulin sensitivity measures compared with placebo, but did not show significant changes in blood pressure and lipid profiles. These findings suggest that optimizing magnesium levels earlier in overweight nondiabetic people may help to prevent insulin resistance and type 2 diabetes.

To improve heart rate variability in patients with heart failure
A small randomized controlled study evaluated the effect of magnesium on stabilized heart failure patients who were discharged from the hospital. Patients were to take the prescribed magnesium supplement for 5 weeks. After this time period, magnesium levels in the blood and intracellularly (considered a more relevant measure) increased significantly in the magnesium-treated group. Heart rate variability also improved, suggesting magnesium supplementation may be beneficial to patients with heart failure.

Magnesium supplements or magnesium-containing antacids and laxatives can interact with many drugs, including antibiotics and medications for chronic diseases such as diabetes and heart disease. Magnesium levels in the body can also be affected by numerous prescription drugs, including the long-term use of drugs commonly used to treat digestive disorders. If you are under treatment for a medical condition, have a complicated medical history, or are in frail condition, you should discuss any magnesium supplements or antacids that you are taking with your doctor.